PACCE: Panitumumab Advanced Colorectal Cancer Evaluation Study

PACCE: A Randomized, Open-Label, Controlled, Clinical Trial of Chemotherapy and Bevacizumab With and Without Panitumumab in the First-Line Treatment of Subjects With Metastatic Colorectal Cancer

The purpose of this study is to assess whether treatment with the study drug, panitumumab given concomitantly with every 2 (Q2) week oxaliplatin-based chemotherapy and bevacizumab improves progression-free survival (PFS) compared to treatment Q2-week with oxaliplatin-based chemotherapy and bevacizumab alone. All subjects will receive Q2-week oxaliplatin- or irinotecan-based chemotherapy and bevacizumab. Control arm subjects will not receive concomitant panitumumab therapy.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Oxaliplatin Based Chemotherapy; Drug: Bevacizumab; Drug: Panitumumab; Drug: Irinotecan Based Chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 1053
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adenocarcinoma of the colon or rectum
• Metastatic colorectal cancer (mCRC)
• Measurable disease per modified response evaluation criteria in solid tumors (RECIST) criteria
• ECOG performance status of 0 or 1
• Available paraffin-embedded tumor tissue (from primary tumor or metastasis) or unstained slides of paraffin-embedded tissue

• If history of other primary cancer, subject will be eligible only if she or he has:

  • Curatively resected non-melanomatous skin cancer;
  • Curatively treated cervical carcinoma in situ;
  • Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 5 years.

• Adequate hematologic data as follows:

  • Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9 cells/L;
  • Platelet count greater than or equal to 100 x 10^9/L;
  • Hemoglobin greater than or equal to 9.0 g/dL. - Adequate renal function:
  • Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN);
  • Urinary protein dipstick of less than 2+ (if urinary dipstick 2+ or greater, then excretion of less than or equal to 1000 mg of protein per day as determined by 24-hour urine collection).

• Adequate hepatic function:

  • Alkaline phosphatase less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
  • Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase)(AST) less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
  • Alanine aminotransferase (serum glutamic-pyruvic transaminase) (ALT) less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
  • Bilirubin less than or equal to 2 x ULN. - Competent to comprehend, sign, and date an IRB-approved informed consent form
• Before any study-specific procedure, the appropriate written informed consent must be obtained.

Exclusion Criteria:

• Prior chemotherapy or biologic (i.e., antibody or vaccine) treatment for mCRC disease - Last dose of adjuvant or radiosensitizing chemotherapy less than 6 months before randomization - Radiotherapy within 14 days before randomization
• Elective and/or planned major surgical procedure to be performed during the course of this trial (surgery that arises as needed or necessary during the course of the study, not agreed a priori, will not make the subject ineligible)
• Major surgery within 28 days before randomization
• Central nervous system metastases
• History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest X-ray or CT-scan
• Clinically significant ascites
• Preexisting bleeding diathesis or coagulopathy or the need for full-dose anticoagulation

• Any of the following within 1 year before randomization:

  • Myocardial infarction;
  • Unstable angina;
  • Symptomatic congestive heart failure;
  • Serious uncontrolled cardiac arrhythmia;
  • Cerebrovascular accident or transient ischemic attack;
  • Gastrointestinal ulcer or hemorrhage;
  • Hemoptysis;
  • Pulmonary embolism;
  • Deep vein thrombosis, or other significant thromboembolic event.
• Regular use of non-steroidal anti-inflammatory agents
• Female subject of childbearing potential, not abstinent, and not willing to use contraceptives during the course of the study and for 6 months following the last dose of first-line treatment
• Female subject who is breast-feeding or who has positive serum pregnancy test 72 hours prior to randomization
• Male subject, not abstinent, and not willing to use adequate contraception upon enrollment into this study and for 6 months following the last dose of first-line treatment
• Subject known to be human immunodeficiency virus (HIV) positive
• Subject allergic to panitumumab or any components of panitumumab formulation
• History of any medical or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results
• Subject unwilling or unable to comply with study requirements
• Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oxaliplatin and bevacizumab without panitumumab; Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone.	Drug: Oxaliplatin Based Chemotherapy; Oxaliplatin-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) consisting of Oxaliplatin, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.; Other Names: Oxaliplatin; FOLFOX 4; FOLFOX 5; Modified FOLFOX 6; FOLFOX 7; Drug: Bevacizumab; Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .; Other Names: Avastin
Experimental: Irinotecan and bevacizumab plus panitumumab; Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W	Drug: Bevacizumab; Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .; Other Names: Avastin; Drug: Panitumumab; PanitumumabPanitumumab is a high affinity (Kd = 5 x 10-11 M) fully human IgG2 monoclonal antibody that is directed against the human EGFr. Panitumumab will be administered by a 30-60 minute IV infusion at a dose of 6 mg/kg once every 2 weeks on the same day of the oxaliplatin- or irinotecan-based chemotherapy and bevacizumab.; Other Names: Vectibix; pmab; Drug: Irinotecan Based Chemotherapy; Irinotecan-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) - Irinotecan, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.; Other Names: FOLFIRI; Douillard
Active Comparator: Irinotecan and bevacizumab without panitumumab; Irinotecan-based chemotherapy and Bevacizumab Q2W alone	Drug: Bevacizumab; Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .; Other Names: Avastin; Drug: Irinotecan Based Chemotherapy; Irinotecan-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) - Irinotecan, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.; Other Names: FOLFIRI; Douillard
Experimental: Oxaliplatin and bevacizumab plus panitumumab; Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W	Drug: Oxaliplatin Based Chemotherapy; Oxaliplatin-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) consisting of Oxaliplatin, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.; Other Names: Oxaliplatin; FOLFOX 4; FOLFOX 5; Modified FOLFOX 6; FOLFOX 7; Drug: Bevacizumab; Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .; Other Names: Avastin; Drug: Panitumumab; PanitumumabPanitumumab is a high affinity (Kd = 5 x 10-11 M) fully human IgG2 monoclonal antibody that is directed against the human EGFr. Panitumumab will be administered by a 30-60 minute IV infusion at a dose of 6 mg/kg once every 2 weeks on the same day of the oxaliplatin- or irinotecan-based chemotherapy and bevacizumab.; Other Names: Vectibix; pmab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (Oxaliplatin)	Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression	Overall study
Objective Tumor Response Through Week 12 (Irinotecan)	Objective tumor response (complete or partial) rate through week 12 based on central review in the Irinotecan stratum	Overall Study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (Oxaliplatin)	Kaplan-Meier estimate of the median time from randomization to death from any cause in groups treated with Oxaliplatin	Overall study
Objective Tumor Response Rate (Oxaliplatin)	Best overall response of complete or partial response within oxaliplatin stratum	Overall study
Time to Progression (Oxaliplatin)	Kaplan-Meier estimate of the median time from randomization to disease progression or death due to disease progression within the oxaliplatin stratum	Overall Study
Time to Treatment Failure (Oxaliplatin)	Kaplan-Meier estimate of the median time from randomization to the date the decision was made to discontinue treatment for a reason other than a complete response to treatment within the oxaliplatin stratum.	Overall study
Overall Survival (Irinotecan)	Incidence of mortality from any cause in groups treated with Irinotecan. Incidence is provided in lieu of the median time to death since the median or its measure of dispersion was not estimable for at least one treatment arm.	Overall study
Progression-free Survival (Irinotecan)	Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression	Overall Study
Objective Tumor Response Rate (Irinotecan)	Best overall response of complete or partial response within irinotecan stratum	Overall Study
Time to Progression (Irinotecan)	Kaplan-Meier estimate of the median time from randomization to disease progression or death due to disease progression within the irinotecan stratum	Overall Study
Time to Treatment Failure (Irinotecan)	Kaplan-Meier estimate of the median time from randomization to the date the decision was made to discontinue treatment for a reason other than a complete response to treatment within the irinotecan stratum	Overall Study

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Abdel-Rahman O. Effect of Body Mass Index on 5-FU-Based Chemotherapy Toxicity and Efficacy Among Patients With Metastatic Colorectal Cancer; A Pooled Analysis of 5 Randomized Trials. Clin Colorectal Cancer. 2019 Dec;18(4):e385-e393. doi: 10.1016/j.clcc.2019.07.005. Epub 2019 Jul 15.
• Abdel-Rahman O. Impact of Sex on Chemotherapy Toxicity and Efficacy Among Patients With Metastatic Colorectal Cancer: Pooled Analysis of 5 Randomized Trials. Clin Colorectal Cancer. 2019 Jun;18(2):110-115.e2. doi: 10.1016/j.clcc.2018.12.006. Epub 2018 Dec 28.
• Hecht JR, Mitchell E, Chidiac T, Scroggin C, Hagenstad C, Spigel D, Marshall J, Cohn A, McCollum D, Stella P, Deeter R, Shahin S, Amado RG. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol. 2009 Feb 10;27(5):672-80. doi: 10.1200/JCO.2008.19.8135. Epub 2008 Dec 29.

Helpful Links

• AmgenTrials clinical trials website
• FDA-approved Drug Labeling

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2005
• Primary Completion (Actual): May 31, 2007
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: June 26, 2005
• First Submitted That Met QC Criteria: June 26, 2005
• First Posted (Estimate): June 27, 2005

Study Record Updates

• Last Update Posted (Actual): October 17, 2018
• Last Update Submitted That Met QC Criteria: September 20, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Cancer; Oncology; Metastatic Colorectal Cancer; Immunex, Abgenix, Amgen; Panitumumab, ABX-EGF; Panitumumab Advanced Colorectal Cancer Evaluation Study (PACCE Study); Colorectal, Colon, Rectal Cancer, Metastatic Colorectal; EGFr, Clinical Trial
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Topoisomerase I Inhibitors; Oxaliplatin; Bevacizumab; Irinotecan; Panitumumab
• Other Study ID Numbers: 20040249